This project is directed towards te development of a novel preclinical model of depression in the laboratory rat. The basis of the depression model is a chronic stress procedure which is of three weeks duration, involving repeated administrations of unpredictable short duration aversive stimuli. At the close of the stress procedure, depression is evaluated in an open field (based upon reduced activity) and based upon a persistent basal endocrine abnormality (elevated plasma corticosterne). Heretofore, the syndrome has proved reversible by antidepressant treatment but not by other drugs. We propose to further assess the validity of the model using novel and established therapeutic interventions (e.g., electroshock, mianserine, bupropion) and other ineffective treatments (neuroleptics, antihistaminic drugs) to evaluate its specificity.